MACBETH Study

Background of the study

Progress has been made in the treatment of metastatic colorectal cancer with the introduction of new targeted agents. Clinical experience and results of scientific research have taught that only a subset of patients may benefit from receiving a class of drugs: anti-EGFR monoclonal antibodies, cetuximab and panitumumab. In particular, the evidence of the role of RAS mutations in predicting intrinsic resistance to these drugs lead to mark a first major step towards tailoring the treatment in metastatic colorectal cancer.
In addition, a study coordinated by our group, the TRIBE study, showed that the association of the three chemotherapy drugs active in this disease: fluorouracil, irinotecan, and oxaliplatin (FOLFOXIRI), in combination with bevacizumab allows to obtain better results in terms of efficacy than the combination of two chemotherapy plus bevacizumab.
Today no robust evidence is available about the combination of the same intensified chemotherapy regimen (FOLFOXIRI) with anti-EGFR drugs.
Another question still debated is what to do after a first phase of more intensive treatment: today is common to continue with a maintenance therapy, aiming at consolidating results obtained in the first phase of therapy, with a lower burden of adverse events. The usefulness of continuing the anti-EGFR drug in maintenance phase is not clear, and is also an open question what is the “best maintenance” to be proposed to patients who have received chemotherapy plus an anti-EGFR drug as induction treatment.



Aim of the study

The goal of the study is to evaluate the activity, efficacy and the safety profile of a therapeutic strategy including the association of FOLFOXIRI plus cetuximab, in patients with metastatic colorectal cancer whose tumors do not bear mutations in RAS and BRAF genes. After a first so-called induction phase in which all patients receive FOLFOXIRI and cetuximab, two different maintenance strategies are investigated: the continuation of cetuximab or the use of bevacizumab, another important molecular target drug with antiangiogenic activity.

The first results presented on XVIII┬░ AIOM Congress; Rome 28-29-30 October 2016: